DESCRIPTION: (Applicant's Abstract) M cells (membranous epithelial cells) are essential participants in immunological receptivity phenomena of most mucosae. Cells with the distinctive morphological and physiological phenotype of M cells have been found in the epithelium overlying mucosa-associated lymphoid tissue in the intestine, bronchi, nasal cavity, and tonsils. M cells initiate mucosal immune events by preferentially binding and translocating soluble and particulate antigens across the surface epithelium and delivering captured antigens to underlying antigenpresenting cells. The follicle-associated epithelium in the mammalian conjunctiva has cells with striking morphological similarity to intestinal M cells but a lack of data on the ability of these cells to transport antigens or pathogens has led some investigators to question their existence in the conjunctiva. We have identified an innovative approach in which an attenuated Shigella strain's natural ability to selectively bind and translocate across M cells can be used to unequivocally demonstrate that the conjunctiva contains fully functional M cells. Multiple species will be examined to establish the ubiquity of M cells in the mammalian conjunctiva. The effect of aging on M cell morphology and function will be also investigated. We will seek to demonstrate ocular immunization is optimal for generating local mucosal immunity by comparing the immune response to ocular topical and intra-nasal immunization with an M-cell targeted immunogen. Demonstration that there are M cells capable of antigen sampling in the conjunctiva will link ocular immunology to the growing body of research concerned with targeted mucosal vaccines. Our long-term goals include designing M-cell targeted vaccines to develop ocular immunity against common ocular pathogens such as Chlamydia trachomatis. Recognition of conjunctival M cells would also lay the foundation for future studies examining whether opportunistic bacterial or viral pathogens use the M cell as an entry site to cross the mucosal barrier in the eye.